Novel approaches to glioma drug design and drug screening

Expert Opinion on Drug Discovery

Volumn 8, Issue 9, 2013, Pages 1135-1151

  Patil, Shivaputra A ^a   Hosni Ahmed, Amira ^a   Jones, Terreia S ^a   Patil, Renukadevi ^a   Pfeffer, Lawrence M ^b   Miller, Duane D ^a  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b UNIVERSITY OF TENNESSEE COLLEGE OF MEDICINE   (United States)

Author keywords

Chemotherapy; Drug delivery; Glioma stem cells; Gliomas; High throughput screening

Indexed keywords

2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; CARBOPLATIN; CARMUSTINE; CILENGITIDE; CROLIBULIN; DELTA8 TETRAHYDROCANNABINOL; ERLOTINIB; GEFITINIB; IMATINIB; IRINOTECAN; LAPATINIB; LOMUSTINE; PACLITAXEL; PAZOPANIB; PERIFOSINE; PROCARBAZINE; SORAFENIB; SUNITINIB; TANDUTINIB; TEMOZOLOMIDE; TIPIFARNIB; TOPOTECAN; VANDETANIB; VATALANIB;

CANCER CHEMOTHERAPY; CANCER RESISTANCE; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG RESEARCH; DRUG SCREENING; GLIOMA; HIGH THROUGHPUT SCREENING; PRIORITY JOURNAL; REVIEW; STEM CELL;

EID: 84882933825     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2013.807248     Document Type: Review

References (127)

1. Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol 2012;14(Suppl 5):v1-49
2. Louis DN, Ohgaki H, Wiestler OD, et al. editors. The 2007 WHO classification of tumours of the central nervous system. IARC Press; Lyon, France; 2007
3. Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes Dev 2007;21(21):2683-710 (Pubitemid 350070717)
4. Siebzehnrubl FA, Reynolds BA, Vescovi A, et al The origins of glioma: E Pluribus Unum? Glia 2011;59(8):1135-47
5. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-96 (Pubitemid 40349501)
6. Ningaraj NS. Drug delivery to brain tumors: Challenges and progress. Expert Opin Drug Deliv 2006;3:499-509
7. Black KL, Ningaraj NS. Modulation of brain tumor capillaries for enhanced drug delivery selectively to brain tumor. Cancer Contr 2004;11:65-73
8. Liu X, Chang Y, Reinhart PH, Sontheimer H. Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells. J Neurosci 2002;22:1840-9 (Pubitemid 35386302)
9. Calatozzolo C, Gelati M, Ciusani E, et al. Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neuro Oncol 2005;74:113-21 (Pubitemid 41478906)
10. Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006;444:756-60 (Pubitemid 44949604)
11. Jamal M, Rath BH, Tsang PS, et al. The brain microenvironment preferentially enhances the radioresistance of CD133 (+) glioblastoma stem-like cells. Neoplasia 2012;14:150-8
12. Eramo A, Ricci-Vitiani L, Zeuner A, et al. Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ 2006;13:1238-41 (Pubitemid 43905604)
13. Liu G, Yuan X, Zeng Z, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 2006;5:67
14. Gown AM. Current issues in ER and HER2 testing by IHC in breast cancer. Mod Pathol 2008;21(Suppl 2):S8-S15 (Pubitemid 351592775)
15. Kitange GJ, Carlson BL, Schroeder MA, et al. Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts. Neuro Oncol 2009;11(3):281-91
16. Newlands ES, Stevens MF, Wedge SR, et al. Temozolomide: A review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev 1997;23:35-61 (Pubitemid 27273454)
17. Solero CL, Monfardini S, Brambilla C, et al. Controlled study with Bcnu v Ccnu as adjuvant chemotherapy following surgery plus radiotherapy for glioblastoma multiforme. Cancer Clin Trials 1979;2:43-8 (Pubitemid 10038636)
18. Walker MD. Chemotherapy: Adjuvant to surgery and radiation therapy. Semin Oncol 1975;2:69-72
19. Walker MD, Green SB, Byar DP, et al. Randomized comparisons of adiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 1980;303:1323-9 (Pubitemid 11194457)
20. Erdem-Eraslan L, Gravendeel LA, de Rooi J, et al. Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: A report from EORTC study 26951. J Clin Oncol 2013;31(3):328-36
21. Yung WK, Mechtler L, Gleason MJ. Intravenous carboplatin for recurrent malignant glioma: A phase II study. J Clin Oncol 1991;9:860-4
22. Warnick RE, Prados MD, Mack EE, et al. A phase II study of intravenous carboplatin for the treatment of recurrent gliomas. J Neurooncol 1994;19:69-74 (Pubitemid 24258542)
23. Carpentier A. Neuro-oncology: The growing role of chemotherapy in glioma. Lancet Neurol 2005;4:4-5 (Pubitemid 40023224)
24. Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009;27:740-5
25. Nghiemphu PL, Liu W, Lee Y, et al. Bevacizumab and chemotherapy for recurrent glioblastoma: A single-institution experience. Neurology 2009;72:1217-22
26. Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: Efficacy, toxicity, and patterns of recurrence. Neurology 2008;70:779-87
27. Readon DA, Dejardins A, Vredenburgh JJ, et al. Metronomic chemotherapy with daily oral etoposide plus bevacizumab for recurrent malignant glioma: A phase II study. Br J Cancer 2009;101:1986-94
28. Zuniga RM, Torcuator R, Jain R, et al. Efficacy, safety and patterns and recurrence in patients with recurrent high grade gliomas treated with bevacizumab plus irinotecan. J Neurooncol 2009;91:329-36
29. Vredenburgh JJ, Desjardins A, Herndon JE II, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25:4722-9 (Pubitemid 350086473)
30. Dowell J, Minna JD, Kirkpatrick P. Erlotinib hydrochloride. Nat Rev Drug Discov 2005;4:13-14 (Pubitemid 40109581)
31. Barker AJ, Gibson KH, Grundy W, et al. Studies leading to the identification of ZD1839 (IressaTM): An orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg Med Chem Lett 2001;11:1911-14 (Pubitemid 32675316)
32. Rich JN, Reardon DA. Peery T, et al. phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 2004;22:133-42 (Pubitemid 41095125)
33. Capdeville R, Buchdunger E, Zimmermann J, et al. Glivec (ST1571, Imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 2002;1(7):493-502
34. Wen PY, Yung WK, Lamborn KR, et al. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium study 99-08. Clin Cancer Res 2006;12:4899-907 (Pubitemid 44338577)
35. Reardon DA, Egorin MJ, Quinn JA, et al. Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme. J Clin Oncol 2005;23:9359-68
36. Sathornsumetee S, Rich JN. Designer therapies for glioblastoma multiforme. Ann NY Acad Sci 2008;1142:108-32
37. Kreisl TN. Chemotherapy for malignant gliomas. Semin Radiat Oncol 2009;19:150-4
38. Li Q-Y, Zu Y-G, Shi R-G, Yao L-P. Review camptothecin: Current perspectives. Curr Med Chem 2006;13:2021-39
39. Vredenburgh JJ, Desjardins A, Reardon DA, Friedman HS. Experience with irinotecan for the treatment of malignant glioma. Neuro-oncol 2009;11:80-91
40. Quinn JA, Jiang SX, Reardon DA, et al. Phase II trial of temozolomide (TMZ) plus irinotecan (CPT-11) in adults with newly diagnosed glioblastoma multiforme before radiotherapy. J Neurooncol 2009;95(3):393-400
41. Quinn JA, Jiang SX, Reardon DA, et al. Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. Cancer 2009;115(13):2964-70
42. Prados MD, Lamborn K, Yung WKA, et al. A phase 2 trial of irinotecan (CPT- 11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study. Neuro-Oncol 2006;8:189-93 (Pubitemid 46542664)
43. Koukourakis MI, Giatromanolaki A, Schiza S, et al. Concurrent twice-a-week docetaxel and radiotherapy: A dose escalation trial with immunological toxicity evaluation. Int J Radiat Oncol Biol Phys 1999;43:107-14 (Pubitemid 29065839)
44. Geney R, Ungureanu LM, Li D, Ojima I. Overcoming multidrug resistance in taxane chemotherapy. Clin Chem Lab Med 2002;40(9):918-25 (Pubitemid 35277418)
45. Turk D, Hall MD, Chu BF, et al. Identification of compounds selectively killing multidrug-resistant cancer cells. Cancer Res 2009;69(21):8293-301
46. Nabors LB, Mikkelsen T, Rosenfeld SS, et al. Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 2007;25:1651-7 (Pubitemid 46797943)
47. Nabors L, Rosenfeld S, Mikkelsen T, et al. NABTT 9911: A phase I trial of EMD 121974 for treatment of patients with recurrent malignant gliomas. Neuro-oncol 2004;6(4):379
48. Eskens FA, Dumez H, Hoekstra R, et al. Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours. Eur J Cancer 2003;39:917-26 (Pubitemid 36428623)
49. Reardon D, Fink K, Nabors B, et al. Phase IIa trial of cilengitide (EMD121974) single-agent therapy in patients (pts) with recurrent glioblastoma (GBM): EMD 121974-009. J Clin Oncol 2007;25(Suppl 18):2002
50. Gilbert MR, Kuhn J, Lamborn KR, et al. Cilengitide in patients with recurrent glioblastoma: The results of NABTC 03-02, a phase II trial with measures of treatment delivery. J Neurooncol 2012;106(1):147-53
51. Reardon DA, Fink KL, Mikkelsen T, et al. Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 2008;26(34):5610-17
52. Sarfaraz S, Adhami VM, Adhami DN, et al. Cannabinoids for Cancer Treatment: Progress and Promise. Cancer Res 2008;68:339-42 (Pubitemid 351380057)
53. Isakovic A, Jankovic T, Harhaji L, et al. Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. Bioorg Med Chem 2008;16:5683-94 (Pubitemid 351699277)
54. Stevens MF, Hickman JA, Stone R, et al. Antitumor imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2- chloroethyl)imidazo[5,1-d]-1,2,3,5- tetrazin-4(3 H)-one, a novel broad-spectrum antitumor agent. J Med Chem 1984;27:196-201 (Pubitemid 14178871)
55. Patil R, Patil S, Wang XD, et al. Synthesis and evaluation of new 1,2,3,4-tetrahydroisoquinoline analogs as antiglioma agents. Med Chem Res 2011;20(1):131-7
56. Patil SA, Wang J, Li XS, et al. New substituted 4H-chromenes as anticancer agents. Bioorg Med Chem Lett 2012;22(13):4458-61
57. Zagotto G, Redaelli M, Pasquale R, et al. 8-Hydroxynaphthalene-1,4-dione derivative as novel compound for glioma treatment. Bioorg Med Chem Lett 2011;21:2079-82
58. Huang H-S, Huang H-F, Yeh P-F, et al. Structure-based design and synthesis of regioisomeric disubstituted aminoanthraquinone derivatives as potential anticancer agents. Hel Chem Acta 2004;87:999-1006 (Pubitemid 38596112)
59. Mun J, Jabbar AA, Devi NS, et al. Design and in vitro activities of N-Alkyl- N-[(8-R-2,2-dimethyl-2Hchromen-6-yl) methyl]heteroarylsulfonamides, novel, small-molecule hypoxia inducible factor-1 pathway inhibitors and anticancer agents. J Med Chem 2012;55:6738-50
60. Hudkins RL, Becknell NC, Zulli AL, et al. Synthesis and biological profile of the pan-Vascular Endothelial Growth Factor Receptor/Tyrosine Kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGFR/ TIE-2) Inhibitor 11-(2-Methylpropyl)- 12,13-dihydro-2-methyl-8-(pyrimidin-2- ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4- c]carbazol-4-one (CEP-11981): A novel oncology therapeutic agent. J Med Chem 2012;55:903-13
61. Comes Franchini M, Bonini BF, Camaggi CM, et al. Design and synthesis of novel 3,4-disubstituted pyrazoles for nanomedicine applications against malignant gliomas. Eur J Med Chem 2010;45:2024-33
62. Lipinski CA, LombardoF, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev 1997;23:3-25 (Pubitemid 27046991)
63. Li Y, Huang W, Huang S, et al. Screening of anti-cancer agent using zebrafish: Comparison with the MTT assay. Biochem Biophys Res Commun 2012;422:85-90
64. Wilson JK, Sargent JM, Elgie AW, et al. A feasibility study of the MTT assay for chemosensitivity testing in ovarian malignancy. Br J Cancer 1990;62:189-94 (Pubitemid 20242433)
65. Romijn JC, Verkoelen CF, Schroeder FH. Application of the MTT assay to human prostate cancer cell lines in vitro: Establishment of test conditions and assessment of hormone-stimulated growth and drug-induced cytostatic and cytotoxic effects. Prostate 1988;12:99-110
66. Hosni-Ahmed A, Barnes JD, Wan J, Jones TS. Thiopurine methyltransferase predicts the extent of cytotoxicty and DNA damage in astroglial cells after thioguanine exposure. PLoS One 2011;6:e29163
67. Hagg M, Biven K, Ueno T, et al. A novel high-through-put assay for screening of pro-apoptotic drugs. Invest New Drugs 2002;20:253-9 (Pubitemid 34823753)
68. Antczak C, Takagi T, Ramirez CN, et al. Live-cell imaging of caspase activation for high-content screening. J Biomol Screen 2009;14:956-69
69. Krutzik PO, Nolan GP. Fluorescent cell barcoding in flow cytometry allows high-throughput drug screening and signaling profiling. Nat Methods 2006;3:361-8
70. Farkas T, Hoyer-Hansen M, Jaattela M. Identification of novel autophagy regulators by a luciferase-based assay for the kinetics of autophagic flux. Autophagy 2009;5:1018-25
71. McCulloch MW, Coombs GS, Banerjee N, et al. Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives. Bioorg Med Chem 2009;17:2189-98
72. Macarron R, Banks MN, Bojanic D, et al. Impact of high-throughput screening in biomedical research. Nat Rev Drug Discov 2011;10:188-95
73. Stahura FL, Bajorath J. Virtual screening methods that complement HTS. Comb Chem High Throughput Screen 2004;7:259-69 (Pubitemid 38858880)
74. Ivascu A, Kubbies M. Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis. J Biomol Screen 2006;11:922-32 (Pubitemid 44847146)
75. Goldstein DM, Gray NS, Zarrinkar PP. High-throughput kinase profiling as a platform for drug discovery. Nat Rev Drug Discov 2008;7:391-7 (Pubitemid 351619111)
76. Available from: Http://dtp.nci.nih.gov/ docs/misc/common-files/cell-list. html
77. Decker S, Hollingshead M, Bonomi CA, et al. The hollow fibre model in cancer drug screening: The NCI experience. Eur J Cancer 2004;40:821-6 (Pubitemid 38519760)
78. Lee KH, Rhee KH. Correlative effect between in vivo hollow fiber assay and xenografts assay in drug screening. Cancer Res Treat 2005;37:196-200
79. Chan XH, Nama S, Gopal F, et al. Targeting glioma stem cells by functional inhibition of a prosurvival oncomiR-138 in malignant gliomas. Cell Rep 2012;2:591-602
80. Brown CE, Starr R, Aguilar B, et al. Stem-like tumor-initiating cells isolated from IL13Ralpha2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells. Clin Cancer Res 2012;18:2199-209
81. Choi BD, Kuan CT, Cai M, et al. Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma. Proc Natl Acad Sci USA 2013;110:270-5
82. Mehta S, Huillard E, Kesari S, et al. The central nervous system-restricted transcription factor Olig2 opposes p53 responses to genotoxic damage in neural progenitors and malignant glioma. Cancer Cell 2011;19:359-71
83. Papagiannakopoulos T, Friedmann-Morvinski D, Neveu P, et al. Pro-neural miR-128 is a glioma tumor Novel approaches to glioma drug design and drug screening suppressor that targets mitogenic kinases. Oncogene 2012;31:1884-95
84. Squatrito M, Vanoli F, Schultz N, et al. 53BP1 is a haploinsufficient tumor suppressor and protects cells from radiation response in glioma. Cancer Res 2012;72:5250-60
85. Kemper EM, Leenders W, Kusters B, et al. Development of luciferase tagged brain tumour models in mice for chemotherapy intervention studies. Eur J Cancer 2006;42:3294-303 (Pubitemid 44854510)
86. Weizsacker M, Nagamune A, Winkelstroter R, et al. Radiation and drug response of the rat glioma RG2. Eur J Cancer Clin Oncol 1982;18:891-5 (Pubitemid 12004632)
87. Miknyoczki S, Chang H, Grobelny J, et al. The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity. Mol Cancer Ther 2007;6:2290-302 (Pubitemid 47294757)
88. Wang W, Tai CK, Kershaw AD, et al. Use of replication-competent retroviral vectors in an immunocompetent intracranial glioma model. Neurosurg Focus 2006;20:E25
89. Claes A, Wesseling P, Jeuken J, et al. Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization. Mol Cancer Ther 2008;7:71-8
90. Zhang M, Herion TW, Timke C, et al. Trimodal glioblastoma treatment consisting of concurrent radiotherapy, temozolomide, and the novel TGF-beta receptor I kinase inhibitor LY2109761. Neoplasia 2011;13(6):537-49
91. Antunes L, Angioi-Duprez KS, Bracard SR, et al. Analysis of tissue chimerism in nude mouse brain and abdominal xenograft models of human glioblastoma multiforme: What does it tell us about the models and about glioblastoma biology and therapy? J Histochem Cytochem 2000;48:847-58 (Pubitemid 30366619)
92. Gates BJ, DeLuca M. The production of oxyluciferin during the firefly luciferase light reaction. Arch Biochem Biophys 1975;169:616-21
93. Bowie LJ, Irwin R, Loken M, et al. Excited-state proton transfer and the mechanism of action of firefly luciferase. Biochemistry 1973;12:1852-7
94. Uhrbom L, Nerio E, Holland EC. Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nat Med 2004;10:1257-60 (Pubitemid 39540445)
95. Yang M, Reynoso J, Jiang P, et al. Transgenic nude mouse with ubiquitous green fluorescent protein expression as a host for human tumors. Cancer Res 2004;64:8651-6 (Pubitemid 39552079)
96. Vogelstein B, Kinzler KW. The multistep nature of cancer. Trends Genet 1993;9:138-41 (Pubitemid 23098782)
97. Dai C, Celestino JC, Okada Y, et al. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev 2001;15:1913-25 (Pubitemid 32738621)
98. Chow LM, Endersby R, Zhu X, et al. Cooperativity within and among Pten, p53, and Rb pathways induces high-grade astrocytoma in adult brain. Cancer Cell 2011;19:305-16
99. Lei L, Sonabend AM, Guarnieri P, et al. Glioblastoma models reveal the connection between adult glial progenitors and the proneural phenotype. PLoS One 2011;6:e20041
100. Phillips HS, Kharbanda S, Chen R, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 2006;9:157-73 (Pubitemid 43357943)
101. Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17:98-110
102. Uhrbom L, Hesselager G, Nister M, Westermark B. Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus. Cancer Res 1998;58:5275-9 (Pubitemid 28551098)
103. Uhrbom L, Hesselager G, Ostman A, et al. Dependence of autocrine growth factor stimulation in platelet-derived growth factor-B-induced mouse brain tumor cells. Int J Cancer 2000;85:398-406 (Pubitemid 30030415)
104. Hambardzumyan D, Amankulor NM, Helmy KY, et al. Modeling Adult Gliomas Using RCAS/t-va Technology. Transl Oncol 2009;2:89-95
105. Libermann TA, Nusbaum HR, Razon N, et al. Amplification and overexpression of the EGF receptor gene in primary human glioblastomas. J Cell Sci Suppl 1985;3:161-72 (Pubitemid 16137526)
106. Ohgaki H, Dessen P, Jourde B, et al. Genetic pathways to glioblastoma: A population-based study. Cancer Res 2004;64:6892-9 (Pubitemid 39330996)
107. Aldape KD, Ballman K, Furth A, et al. Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance. J Neuropathol Exp Neurol 2004;63:700-7 (Pubitemid 38891086)
108. Holland EC, Hively WP, DePinho RA, Varmus HE. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev 1998;12:3675-85 (Pubitemid 29019648)
109. Ding H, Shannon P, Lau N, et al. Oligodendrogliomas result from the expression of an activated mutant epidermal growth factor receptor in a RAS transgenic mouse astrocytoma model. Cancer Res 2003;63:1106-13 (Pubitemid 36278445)
110. Zhu H, Acquaviva J, Ramachandran P, et al. Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis. Proc Natl Acad Sci USA 2009;106:2712-16
111. Cancer Genome Atlas Research N. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455:1061-8
112. Holland EC, Celestino J, Dai C, et al. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet 2000;25:55-7 (Pubitemid 30257036)
113. Uhrbom L, Dai C, Celestino JC, et al. Ink4a-Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt. Cancer Res 2002;62:5551-8
114. Reilly KM, Loisel DA, Bronson RT, et al. Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat Genet 2000;26:109-13
115. Alcantara Llaguno S, Chen J, Kwon CH, et al. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 2009;15:45-56
116. Baker SJ, Fearon ER, Nigro JM, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 1989;244:217-21 (Pubitemid 19110302)
117. Frankel RH, Bayona W, Koslow M, Newcomb EW. p53 mutations in human malignant gliomas: Comparison of loss of heterozygosity with mutation frequency. Cancer Res 1992;52:1427-33
118. De Vries NA, Bruggeman SW, Hulsman D, et al. Rapid and robust transgenic high-grade glioma mouse models for therapy intervention studies. Clin Cancer Res 2010;16:3431-41
119. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997;275:1943-7 (Pubitemid 27148818)
120. Tohma Y, Gratas C, Biernat W, et al. PTEN (MMAC1) mutations are frequent in primary glioblastomas (de novo) but not in secondary glioblastomas. J Neuropathol Exp Neurol 1998;57:684-9 (Pubitemid 28335057)
121. Zheng H, Ying H, Yan H, et al. p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature 2008;455:1129-33
122. Uhrbom L, Nerio E, Holland EC. Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nat Med 2004;10(11):1257-60 (Pubitemid 39540445)
123. Momota H, Nerio E, Holland EC. Perifosine inhibits multiple signaling pathways in glial progenitors and cooperates with temozolomide to arrest cell proliferation in gliomas in vivo. Cancer Res 2005;65(16):7429-35 (Pubitemid 41161277)
124. Haar CP, Hebbar P, Wallace GC IV, et al. Drug resistance in glioblastoma: A mini review. Neurochem Res 2012;37(6):1192-200
125. Schmalz PGR, Shen MJ, Park JK. Treatment resistance mechanisms of malignant glioma tumor stem cells. Cancers 2011;3:621-35
126. Lovén J, Hoke HA, Lin CY, et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 2013;153(2):320-34
127. Li J, Di C, Mattox AK, et al. The future role of personalized medicine in the treatment of glioblastoma multiforme. Pharmgenomics Pers Med 2010;3:111-27